Prof. dr. Dr Andrea Evers, professor of health psychology at Leiden University and Scientific Director of the Institute of Psychology, conducts research into the placebo effect, among other things. She talks about its applications in practice and the advantages it can offer.
Psychoneurobiological influences on health and disease cover a broad field, says Evers. “It concerns questions such as ‘Do stress factors play a role in illness? If so, what role? Can lifestyle protect against chronic diseases?’.” Evers is working on this in Leiden as well as in Delft and Rotterdam in order to stimulate interdisciplinary collaboration between different disciplines. “You cannot solve these kinds of issues by staying in one place within your own discipline,” says Evers. “For this, bridges must be built that not only have a scientific basis, but are also based on contacts with other social partners and by working together with patients.” For example, Evers has an appointment at the Faculty of Industrial Design in Delft. “We use many e-health applications to support patients. This ranges from apps and e-coaching to serious games and virtual reality.” According to Evers, this in fact concerns everything where technology can help to promote the well-being of the citizen. “I use the word ‘well-being’ consciously because it is more than just physical health and includes psychological and social aspects.” A good example of a direct application of the interdisciplinary collaboration is the use of a virtual reality tool in research into the placebo effect. “This allows young doctors and nurses to receive virtual feedback from patients who respond to (non-)verbal cues. With the placebo effect, the doctor-patient relationship is very important and they learn to optimize that.” In addition, it is also possible to learn how to properly explain the nocebo effect, Evers knows. “If patients are very afraid of side effects of drugs, they increase the chance that they will indeed develop side effects by constantly worrying about them. You can try to reduce this by first telling us something in simple language about the nocebo effect and that it can have an influence.”
Placebo effect is expectation effect
Placebo research is one of Evers’ fundamental lines of research. “We look at the placebo effect as a psychological learning mechanism. What does it mean that something that in itself has no active ingredient, nevertheless has certain effects on our well-being in the broad sense (physiological and psychological), purely on the basis of expectations? This is based on learning processes that we can analyze.” Evers explains that the placebo effect is an expectation effect that plays a role in every treatment. “So it is not at all about a substance that does not contain anything, but about all regular treatments that are applied in which the placebo effect has a large share. This is almost always based on a positive expectation. The learning effects that play a role in the placebo effect are based on a number of mechanisms. First of all, the information we get about something, for example that it would work very well, is important for the image. The second mechanism, conditioning, is the most important. Verbal suggestion and other elements only work because one has a certain expectation from the past that something has meaning or quality. Suppose Prof. Scherder says something, then you believe him much sooner than when the immune neighbor says it. We have conditioned expectations that are lifelong determined by our culture and upbringing. The interesting thing is that this process produces all kinds of physiological effects.” Evers illustrates this with an example. “Suppose you have experienced many traumas, for example in a hospital. Then you get a negative effect and a stress reaction every time you come back to a hospital. That is in fact a nocebo effect.” According to Evers, a generalization of an older conditioning can also occur. She gives an example from clinical practice: “In children with rheumatism who are treated with methotrexate, we see that some become very nauseous. Very often they develop aversive reactions. This manifests itself in such a way that if they are given methotrexate on Tuesday, they will already feel nauseous on Monday. This can only be explained with a conditioning mechanism. For some children, however, this goes much further. The methotrexate pills are yellow, and these kids react to anything yellow by screaming. Also on a yellow ball, or something else that actually has a positive appearance. That’s a typical generalization. This also creates an anxiety disorder, for example, and that can be very serious.”
Application in practice
The placebo effect can be used very easily in a hospital, says Evers. “If patients are given a painkiller and know it, they will experience much less pain than if they don’t know it.” The opposite effect of the placebo effect, the nocebo effect, also provides interesting data. “That study started when it was examined how many side effects patients in control groups who had not received treatment reported. It turned out that they reported just as many side effects and also exactly those side effects that are listed in the package insert. Actually, that was not possible, because they had not been given an active ingredient. It has everything to do with how we think we should inform people about side effects, in detail, and thereby create a kind of boomerang effect that actually causes them to get more side effects.” It is also known that when certain (new) conditions are widely discussed (‘hyped’) in the media, this can also lead to a ‘tsunami’ of unwanted effects and side effects. “It is therefore difficult for the government to communicate in the right way,” says Evers. “On the one hand, the seriousness must be emphasized, but on the other hand, people do not want to frighten people and ‘evoke’ all kinds of undesirable effects. So one has to think very carefully about what exactly is communicated in the media.”
Which information?
It seems as if the desired controlled information provision is at odds with shared decision making (SDM). Although SDM is a ‘hot topic’ within medicine and is often quoted or applied, according to Evers it is certainly not an ideal model for all patients. “It is essential that patients are first informed about the placebo and nocebo effect. That is not at all a topic of discussion in the consulting room. However, if you look at the extent to which it contributes to the effectiveness of the interventions, it is distressing that we continue to pretend that the effect is solely due to the medication alone. And that while every doctor knows that the placebo and nocebo effect plays a major role in everything they do and it does matter how something is prescribed and what is told. In addition, I think that the choice should be left to the patient to what extent he or she wants to participate in the decision-making process and what he or she wants to know. Not everyone needs super-detailed explanations about a treatment or intervention, while for others it is essential to prepare for it as best as possible and to be reassured. The provision of information must therefore be tailored to the individual level.” Evers argues in favor of making the information available on a website, especially with regard to the risks and side effects, so that patients can access it and decide for themselves whether they request this information.
Influencing the immune system
Evers and her research group were one of the first to show that the placebo effect works just as well for itching as it does for pain. “If, for example, an antihistamine is given first and then a placebo, it turns out that the same immune response occurs. Although not in the same intensity, there is a clear simulation of the effect on medication as previously found. Thus, physiological processes are influenced by conditioning.” Evers states that this knowledge can be used at three levels: at the patient level, in communication and with the medication. “In the first case, patients can mainly be allowed to focus on the goal they are pursuing with an operation, for example working or playing with their children. That goal leads to a better recovery after the operation. Second, trust within doctor-patient communication is the most important component of the placebo effect. The relationship with the patient is very crucial and openness plays a role in this. Practitioners must be honest: exaggerating effects is not useful, because patients will not (quickly) be more inclined to believe them. It is much stronger, for example, to admit that one does not know. That increases credibility.” Finally, Evers argues that by using the conditioning principle, prescriptions can be made more efficiently. “Now almost always the same dose is given to almost all patients without taking the conditioning principle into account. If you did, you would give a high dose first to wait for the conditioning effect and then repeat the conditioning. This is especially interesting for chronic diseases, such as psoriasis, depression and ADHD. Studies have shown that you can use medication more effectively in this way. This could be very valuable, especially when reducing chronic medication and, for example, weaning off antidepressants. However, there are only about 20 studies in this area worldwide; so there is clearly a need for more research into this.”